POS0194 MORBIDITY AND MORTALITY OF BREAKTHROUGH COVID-19 IN PATIENTS WITH IMMUNE MEDIATED CONDITIONS ON B CELL DEPLETING THERAPIES AND THE EFFECTS OF MONOCLONAL ANTIBODY TREATMENT
Authors: C. Calabrese, E. Kirchner, M. E. Husni, B. Moss, A. Fernandez, Y. Jin, L. Calabrese
Journal: Annals of the Rheumatic Diseases (2022)

Background Among immunocompromised patients with immune mediated inflammatory diseases (IMIDs), those undergoing therapy with B cell depleting agents are among the most vulnerable to both severe COVID-19 disease and sub-optimal response to COVID-19 vaccines(1). Numerous studies have documented suppressed humoral, but relatively maintained cell mediated, responses to COVID-19 vaccines in these patients. However, the clinical significance of such immunity in terms of protection from infection and its sequelae are poorly understood. We have analyzed a large cohort of vaccinated IMIDs patients undergoing B cell depleting therapy for the presence of breakthrough infection and assessed their outcomes. Objectives: To define the frequency and outcomes of COVID-19 breakthrough infection in fully or partially vaccinated IMIDs patients receiving B cell depleting therapies. To assess the characteristics and risk factors for severe outcomes and death. Methods All pharmacy records from within a large health care system were electronically searched for patients undergoing B cell depleting therapies with approved monoclonal antibodies in 2020. Records with ICD codes for IMIDs but not malignancies were included; patients must also have had at least one documented COVID-19 vaccine. From this cohort all patients with breakthrough COVID-19 disease from time of 1st vaccination through December 15, 2021 were identified; each record was hand-reviewed to extract clinical data including vaccine history, demographics, comorbidities, use of monoclonal antibodies, dose and timing of B cell depleting therapy, and outcomes as assessed by an 8 point NIH ordinal scale. Univariate and multivariable logistic/proportional-odds regression models were used to examine the risk factors for severe outcomes. Results A total of 1677 IMIDs patients were identified who received any B cell depleting monoclonal antibody and at least one COVID-19 vaccine in 2021. From this cohort 74 patients (4.4%) experienced a breakthrough COVID-19 infection. Among the breakthrough patients 34 (46%) had a rheumatic disease (RA 11, AAV 15, SLE 2), 34 (46%) had CNS inflammatory disease (MS 32, 2 other), and 6 (8%) had immune hematologic/miscellaneous diseases. Four patients had a previous history of COVID-19 infection. Overall 24 (35%) were hospitalized with 11 patients requiring critical level care (15%) and 6 deaths (8 %). All fatal cases had rheumatic diseases. Monoclonal antibodies were given as outpatient therapy to 21 patients and among these only 1 patient was hospitalized without requiring O2 and none died. In univariate analysis only number of comorbidities had a significant positive effect (p=.001) on severe outcomes (i.e. groups 1-4 vs. groups 5-8: Table 1) while monoclonal antibody therapy was associated with more favorable outcomes (p=.005 group 1-2 vs.3-8, Table 1). There were no associations between the dose, duration or timing of the B cell therapy, concomitant therapies including glucocorticoids, vaccine status (incomplete, complete, boosted) or date of vaccination with severe outcomes. Conclusion In IMIDs patients treated with B cell depleting therapies breakthrough infections are common with many experiencing severe outcomes. Concomitant comorbidities were associated with risk of severe disease. Monoclonal antibody therapy was used in only 28% but was associated with enhanced clinical outcomes with only 1 in 21 requiring hospitalization and zero mortality. This population of immunocompromised patients remains vulnerable to COVID-19 disease despite vaccination. More aggressive use of outpatient management with monoclonal antibody therapy and other preventive and therapeutic measures are urgently needed. Reference [1]Samuel Bitoun et al Rituximab impairs B-cell response but not T-cell response to COVID-19 vaccine in auto-immune diseases First published: 28 December 2021 Arthritis and Rheumatology https://doi.org/10.1002/art.42058 Disclosure of Interests cassandra calabrese Speakers bureau: Sanofi-regeneron, Consultant of: Sanofi-regeneron, Elizabeth Kirchner Consultant of: Janssen, M Elaine Husni Consultant of: Abbvie, BMS, Novartis, Lilly, Pfizer, UCB, Regeneron, Janssen, Brandon Moss Consultant of: Biogen advisory board, Grant/research support from: Genentech/Roche and Novartis as part of investigator-initiated studies, Anthony Fernandez Consultant of: Consulting: AbbVie, Novartis, Mallinckrodt, UCB, BMS, Boehringer Ingelheim, Alexion, Grant/research support from: Research: AbbVie, Novartis, Pfizer, Corbus, Mallinckrodt, Yuxuan Jin: None declared, Leonard Calabrese Speakers bureau: Sanofi, Janssen, AbbVie, ChemoCentryx, GSK, AstraZeneca, Consultant of: Sanofi, Jansen, AbbVie, ChemoCentryx, GSK, AstraZeneca, BMS, Genentech